Fetal and Adult Testis-Expressed 1, encoded by the ''FATE1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
in humans, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
identified as a cancer-testis antigen (CTA) in hepatocellular carcinomas and gastric and colon cancers.
It is testis-specific in the
fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
(aged 6 – 11 weeks). In adults, it is expressed predominantly in the
testis and adrenal glands, with some expression in the lungs, heart, kidneys and throughout the brain.
FATE1 is member of the
Miff
MIFF may refer to:
Film festivals
* Listapad, aka Minsk International Film Festival, held each November in Minsk, Belarus
*Maine International Film Festival, held in Waterville, Maine
*Melbourne International Film Festival, held in Melbourne, Aus ...
protein family, with its C-terminal domain, consisting of a transmembrane domain with a coiled-coil domain, showing high similarity to the
mitochondrial fission factor (MFF) protein which is involved in mitochondrial and peroxisomal fission.
Gene location
''FATE1'' gene in humans is located on the long arm of the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
at region 28, from
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
150,884,502 to base pair 150,891,617.
Mechanism
It has been hypothesized that FATE1 uses its C-terminal transmembrane domain to attach to
endoplasmic reticulum (ER) membrane and with its C-terminal
coiled-coil
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
domain it interacts with mitochondria.
FATE1 is localized in mitochondria-associated ER membranes (MAM) and modulates ER-mitochondria distance to regulate Ca
2+- and drug dependent apoptosis in cancer cells.
FATE1 expression leads to reduction of Ca
2+ uptake by mitochondria and therefore decrease in fragmentation of mitochondria, associated with mitochondrial Ca
2+ uptake, consequently providing protection against cell death.
Relation to cancer
FATE1 is detectable in all cell lines derived from tumors, but is low or undetectable in telomere immortalized, non-tumorigenic fibroblasts and lung epithelial cells. FATE1 is suggested to be essential for survival of tumor cells as depletion of FATE1 results in viability reduction in melanoma, breast, prostate and sarcoma settings.
Upregulation of FATE1 by a transcription factor
steroidogenic factor-1 (SF-1), involved in adrenal and gonadal development as well as in adrenocortical carcinoma, increases ER-mitochondria distance and is utilized by cancer cell to functionally uncouple ER and mitochondria.
Silencing ''FATE1'' gene sensitizes non-small-cell lung cancer cell lines to
paclitaxel
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...
, a chemotherapeutic drug against many different types of cancers.
Elevated level of FATE1 is found to be associated with higher mortality rate in colorectal cancers, but in non-small-cell lung cancers, elevation of FATE1 alone did not decrease chance of survival, but decreased if
RNF183 expression is also increased.
References
Further reading
*
*
*
*
*
*
{{gene-X-stub